Results of a large real-world safety study of combined oral contraception published
LONDON–(COMMERCIAL THREAD) –For medical and commercial / industrial media and investors outside of the United States and Canada only
Theramex, a global women’s health company, today announced that safety results from the PRO-E2 real-world safety study for Zoely® (NOMAC-E2) have been published in The European Journal of Contraception and Reproductive Health Care (EJCRH).1
The Post-Authorization Safety Study (PASS), known as PRO-E2, was a large, prospective, non-interventional, controlled cohort study involving more than 101,000 women. PRO-E2 compared the risks of using NOMAC-E2 versus COCs containing levonorgestrel (COC-LNG), a commonly prescribed contraceptive.1
The main objective of the real-world study was to assess and compare the risk of cardiovascular events * in users of NOMAC-E2 with users of COC-LNG. For the primary clinical outcome, the risk of VTE?? was at least as low with NOMAC-E2 as with COC-LNG, which is consistent with the results of previous studies (0.59 Hazard Ratio [HR]95% confidence interval [CI], 0.25-1.35).1
PRO-E2 also demonstrated that contraceptive failure (risk of unintended pregnancy), a key secondary outcome, was statistically significantly lower with NOMAC-E2 compared to COC-LNG (0.45 HR † , 95% CI, 0.34-0.60, [p<0.0001]). Further analyzes showed that the lower rate of unintended pregnancies with NOMAC-E2 was even more pronounced in women under 35.2 The shorter hormone-free interval with NOMAC-E2, its longer half-life, and its monophasic regimen can all help reduce the number of unintended pregnancies.5.6.7 These results will be published in the EJCRH later this month.
All 14 secondary endpoints of the study were met, with a risk of serious adverse events and depressive disorders or changes in weight or acne score with NOMAC-E2 comparable to COC-LNG.2
Dr Joaquim Calaf Alsina, Honorary Professor of Obstetrics and Gynecology at the Autonomous University of Barcelona, Spain, said: “This is an exciting real-world study that confirms what we suspected at the both the biological profile and the experience of using NOMAC-E2. This contraceptive combination has at least the same risk of VTE as the preparation which has been shown to have the lowest risk in this regard. The data from PRO-E2 also provides patients with important and reassuring data on efficacy and other additional benefits, such as improvement in acne and low impact on body weight.
Ms Claudine Domoney, Consultant Gynecologist, Chelsea & Westminster Hospital, London, UK, said: “Contraception can be difficult for women and as clinicians we want to make it as easy as possible. To do this, there must be a range of options that provide reliable and convenient fertility control. The PRO-E2 study, which reflects the real-life experience of women, confirms that NOMAC-E2 is better at preventing unintended pregnancies than COC-LNG.
Theramex CEO Robert Stewart said, “The results of the PRO-E2 study will boost confidence in what has already proven to be a reliable and effective birth control option. As a company dedicated to improving women’s health, we are delighted that the wealth of evidence from this safety study can help clinicians and women make informed decisions about contraception.
The safety and efficacy publications were accepted by the EJCRH in September. The publication of the safety results is available online:
The efficacy publication will be available online later this month. Both publications will be available in the print journal in December.
The results have also been submitted to the European Medicines Agency (EMA) and will be presented at the congress of the European Society of Gynecology in November this year.
Notes to editor:
About the PRO-E2 study
PRO-E2 was designed to compare the risks of using NOMAC-E2 versus COC-LNG.8.9 VTE is a rare but serious adverse event associated with the use of COCs.10.11 COC-LNG was chosen as the comparator for the study as the COC associated with the lowest risk of VTE, according to treatment guidelines.12
The study, initiated by MSD and conducted by ZEG-Berlin, was requested by the European Medicines Agency (EMA).8 A PASS is performed after a medicine has been authorized to gain additional information about the safety of a medicine or to measure the effectiveness of risk management measures.
The primary outcome measure was the risk of VTE (particularly deep vein thrombosis of the lower limbs and pulmonary embolism).1 Secondary outcomes of interest were: all VTE, arterial thromboembolism, idiopathic VTE, summary of VTE results, depressive disorders, mood changes, gallstones, inflammatory bowel disease , the effect on fertility (contraceptive failure and return to fertility), pregnancy outcomes, weight change, hepatobiliary disorders and acne.2
PRO-E2 was initiated in 2014 (following a pioneering study, CELINA, initiated in 2012) and closed in December 2020.8 The results reflect the actual practice of more than 101,000 women (equivalent to 144,901 data of woman-years) from Australia, Austria, Colombia, France, Germany, Hungary, Italy, Mexico, Poland, Russia, Spain and Sweden.1
About Zoély® (NOMAC-E2)
NOMAC-E2 combines nomegestrol acetate [2.5mg] and 17β-estradiol [1.5mg]. NOMAC-E2 is the only monophasic contraceptive pill using the same 17B-estradiol in the body. Nomegestrol acetate (NOMAC) is a highly selective progestin derived from the natural hormone progesterone.3.4
MSD has been exclusively licensed by Theramex to sell Zoely® in certain territories (other than the United States and Canada) until January 2020 and held marketing authorizations for the product in non-EU markets in that territory. In January 2020, these rights were transferred back to Theramex. The rights to sell the product in the United States and Canada under a license from Teva remained with MSD until the Organon split on June 2, 2021. Zoely® and Stezza® are brand names of NOMAC Nomegestrol Acetate 2.5 mg + 17β-Estradiol E2 1.5 mg Combined Oral Contraception.
With a large portfolio of innovative and established brands covering contraception, fertility, menopause and osteoporosis, we support women at every stage of their lives. Our commitment is to listen and understand our patients, to meet their needs and to offer healthcare solutions to help improve their lives. Our vision is to be a lifelong partner for women and the healthcare professionals who treat them, providing innovative and effective solutions that care for and support women as they move through every stage of their lives. www.theramex.com
Reed S et al. Eur J Contracept Reprod Healthcare. Available at: https://www.tandfonline.com/doi/10.1080/13625187.2021.1987410 Accessed October 2021
PRO-E2 final report. Available at: http://www.encepp.eu/encepp/openAttachment/studyResult/41498;jsessionid=uW82EciuLgcm015Qta9_pO v1_2skaG629DgRqfNG6I5-i02w5oS0! 2052488890
Theramex. (2021) Zoély® RCP. Available at: https://www.medicines.org.uk/emc/product/3038/smpc. Accessed October 2021
Westhoff C et al. ObstetGynecol 2012; 119 (5): 989-99.
Christin-MaîtreS et al. Women’s Health (London) 2013; 9 (1): 13-23.
Van Vliet HAAM, Raps M. Cochrane Database Syst Rev 2011; (11): CD009038.
Duijkers IJM et al. Eur J Contracept Reprod Health Care 2010; 15 (5): 314-25.
Clinicaltrials.gov. (2021) Prospective controlled cohort safety study of a monophasic oral contraceptive containing nomegestrol acetate (2.5 mg) and 17β-estradiol (1.5 mg) (PRO-E2). Available at: https://clinicaltrials.gov/ct2/show/study/NCT01650168 Accessed October 2021
Reed, S. et al. Pharmacoepidemiol Drug Saf. 2020; 29 (Suppl. 3): 4.
United States Food and Drug Administration. (2018). FDA Drug Safety Communication: Updated Information on the Risk of Blood Clots in Women Taking Oral Contraceptives Containing Drospirenone. Available at: www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-information-about-risk-blood-clots-women-taking-birth-control. Accessed October 2021
de Bastos, M. et al. (2014) Cochrane Database Syst Rev (3): CD010813.
Faculty of Sexual and Reproductive Health. FSRH Guideline Combined Oral Contraception. January 2019 (Modified in November 2020).
* In particular deep vein thrombosis of the lower limbs and pulmonary embolism
† HR adjusted for age, body mass index, current duration of hormonal contraceptive use, family history of VTE